Treatment of Dysplasia - Lakareol.com · with treatment of cervical intraepithelial neoplasia:...

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10/29/2011 1 Treatment of Dysplasia Karen Smith-McCune October 26, 2011 Disclosures I am on the Clinical and scientific advisory Board of OncoHealth Inc, a biotech startup that is developing a diagnostic test for cervical cancer screening. Goals Discuss treatment options for cervical dysplasia Review literature about obstetrical outcomes of treatments for CIN Discuss treatment guidelines for adolescents and young women CASE 25 year old G0 is referred for a Pap showing HSIL Colposcopy Biopsy showed CIN 2,3 www.lakareol.com

Transcript of Treatment of Dysplasia - Lakareol.com · with treatment of cervical intraepithelial neoplasia:...

  • 10/29/2011

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    Treatment of Dysplasia

    Karen Smith-McCuneOctober 26, 2011

    Disclosures• I am on the Clinical and scientific advisory

    Board of OncoHealth Inc, a biotech startup that is developing a diagnostic test for cervical cancer screening.

    Goals• Discuss treatment options for cervical

    dysplasia• Review literature about obstetrical outcomes

    of treatments for CIN• Discuss treatment guidelines for adolescents

    and young women

    CASE• 25 year old G0 is referred for a Pap showing

    HSIL• Colposcopy

    Biopsy showed CIN 2,3

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    w.lakareol.com

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    What would you do next?

    • HPV test• Follow-up in 6 months with cytology and

    colposcopy• Treat

    – LEEP– Cone biopsy– Cryotherapy– Laser ablation– Laser cone

    Choice of therapyABLATIVE EXCISIONAL

    Cryotherapy Loop excision

    CO2 laser ablation Laser cone biopsy

    (Electrofulguration, cold coagulation)

    Cold knife cone biopsy

    Advantages of excisional therapy• Allows histological assessment exact grade of

    disease present- hence compensates for inaccuracies in colposcopic impression

    • Allows “see and treat” approach• Allows assessment of margins• Allows the diagnosis of occult cancer

    Choice of therapy: excision versus ablation

    Choice of ablative therapy (cryotherapy, laser ablation) requires that the following conditions are met:– Satisfactory colposcopy and/or negative ECC – lesion fully visualized– no evidence of invasion

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    Choice of therapy: excision versus ablation

    • Isn’t the effectiveness of LEEP or cold knife cone better than cryotherapy?

    Efficacy: Loop vs Cryotherapy vs Laser• Randomized clinical trial of loop versus

    laser vaporization versus cryotherapy• 120-140 patients in each arm• Randomization stratified by lesion size,

    endocervical gland involvement, and SIL grade

    • No difference in complications, recurrence or persistence

    Mitchell et al, 1998 Obstet Gynecol 92; 737-44

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    Why choose ablative therapy?• The preponderance of the evidence suggests

    that excisional therapies are associated with adverse obstetrical outcomes

    Obstetric sequelae of excisional therapy for CIN

    • Retrospective cohort study (Australia)• Risk of pPROM was significantly increased

    following treatment with laser conization (aRR, 2.7) or LEEP (aRR 1.9), but not laser ablation (aRR, 1.1).

    • Not associated with preterm delivery

    Sadler et al 2004 JAMA

    Obstetric sequelae of LEEP• Retrospective cohort study from Halifax Canada• LEEP associated with preterm deliver (7.9% versus

    2.5%)• LEEP associated with preterm delivery after

    premature rupture of membranes (3.5% versus 0.9%)

    Samson et al 2005 Obstet Gynecol

    Obstetric sequelae of excisional therapy for CIN: meta-analysis

    • Systematic review and meta-analysis of obstetric outcomes after excisional therapy for CIN (cone, loop, laser)

    • 27 studies • Preterm birth defined as less than 37 weeks

    Kyrgiou et al Lancet 2006

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    Obstetric sequelae of excisional therapy for CIN: meta-analysis

    • LEEP was significantly associated with:-preterm delivery: 11% vs 7%, -low birthweight (

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    Preterm delivery aftersurgical treatment for CIN

    • Prospective cohort study (Norway) of 11,088 women beginning in 1991

    • 14,982 births• Follow-up through 2004

    Nohr et al 2007 Acta Obstet Gynecol Scanda

    Preterm delivery aftersurgical treatment for CIN

    •Prior preterm birth was strongest risk factor (OR=2.3, 95% CI 1.4-3.7)

    • Incidence of preterm birth was 3.5% in women with no prior LEEP versus 6.6% in women following LEEP (OR 1.8, 95% CI 1.1-2.9)

    Nohr et al Acta Obstet Gynecol Scanda 2007

    Preterm delivery aftersurgical treatment for CIN

    • Retrospective registry study from Finland• 25,827 women with surgical therapy for CIN

    from 1986-2003• 8210 singleton births• Risk of preterm labor increased after cold

    knife/LEEP cone (RR 2.1 fold for

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    Gestational age

    Delivery before 37 weeks: 6.2% no cone17% prior cone 6.7% subsequent cone

    Albrechtson et al, BMJ 2008

    Birth weight

    Albrechtson et al, BMJ 2008

    Relative risk of preterm birth after cone versus no cone- Norway

    Albrechtson et al BMJ 2008

    Perinatal mortality and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial

    neoplasia: meta-analysis• Cold knife cone associated with increased risk

    of: • Preterm delivery

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    Perinatal mortality and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial

    neoplasia: meta-analysis• LEEP was not significantly associated with

    increased risk of perinatal mortality, preterm delivery, or low birth weight

    • Ablative therapies were not significantly associated with increased risk of perinatal mortality, preterm delivery, or low birth weight

    Arbyn et al, BMJ 2008

    • Population based cohort study at Aarhus University Hospital (8% of all Danish births)

    • 721 deliveries after 1 cone, 37 deliveries after 2 cones, 74,552 deliveries after no dysplasia or cones

    • 572 had LEEPs, 71 electrosurgical needles procedure, 67 cold knife cone

    • Outcomes: GA, birth weight, perinatal mortality

    Obstetrical outcomes after excisional procedure- Denmark

    Ortoft et al, 2010 BJOG

    Obstetrical outcomes after excisional procedure- Denmark

    RR for Preterm delivery

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    Obstetrical outcomes after excisional procedure- Denmark

    • The height of the cone was associated with significantly associated with the gestational age at delivery

    • Circumference and volume of the cone were NOT associated with gestational age at delivery

    Ortoft et al, 2010 BJOG

    Depth of cervical cone removed by loop electrosurgical excision procedure and

    subsequent risk of spontaneous preterm delivery: Denmark

    • Registry based study of all deliveries form Denmark from 1999-2005: 552,678 singleton deliveries

    • increasing cone depth was associated with a significant increase in the risk of preterm delivery

    • adjusted odds ratio of 1.06 (1.03-1.09) of preterm birth for each mm of tissue removed

    Noehr et al Obstet Gynecol 2009

    Depth of cervical cone removed by loop electrosurgical excision procedure and

    subsequent risk of spontaneous preterm delivery: Denmark

    • Time since LEEP was not associated with preterm delivery

    • Two or more LEEPs increased the risk almost fourfold for subsequent preterm delivery (versus no LEEP)

    Noehr et al Obstet Gynecol 2009

    Loop electrosurgical excision procedure and risk of preterm birth

    • 241,701 singleton births at Parkland Hospital from 1992-2008– 511 had previously undergone LEEP– 842 subsequently underwent LEEP

    • No increase in preterm birth

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    Obstetrical outcomes after treatment for CIN: Summary of evidence

    • There are no randomized trials• Excisional procedures appear to be associated

    with an increased risk of preterm delivery and perinatal mortality

    • The data on ablative procedures are more limited but do not show a strong association with adverse obstetrical outcomes

    • Depth of excision may be important: deeper is not necessarily better in reproductive aged women

    Choice of therapyABLATIVE EXCISIONAL

    Cryotherapy Loop excision

    CO2 laser ablation Laser cone biopsy

    (Electrofulguration, cold coagulation)

    Cold knife cone biopsy

    Cryosurgery (Cryotherapy)• Historically was the 1st outpatient treatment

    of CIN• Low cost, high patient safety• Easy to perform, well tolerated• Requires stringent patient selection guidelines• Clearance rates for CIN = 86% to 91.6%• Key predictor of success is depth of freeze

    Courtesy E.J. Mayeux

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    Courtesy E.J. Mayeux

    Cryotherapy

    • Success more related to – lesion size than to lesion grade – absence of lesion 4 to 5 mm into canal

    • Other than large lesion size and extension into the canal, treatment failure is most commonly secondary to inadequate freeze

    Cryotherapy

    • Goal is top create sufficient thermal injury to kill abnormal cells

    • -20 degrees Celsius necessary for cell death• For successful ablation, goal is to freeze

    beyond the lesion

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    Cryotherapy• “Iceball” = freeze depth = lateral spread• Most tissue in this zone will necrose

    Cervix

    Cryoprobe

    Courtesy E.J. Mayeux

    Cryotherapy• CIN may penetrate glands 3.6-3.8mm• Cell death to 4mm eradicates 99.7% of

    lesions• Goal: 5mm iceball with a double freeze

    Cryotherapy

    • After treatment, copious watery vaginal discharge for up to one month is common

    • Bleeding and infection are rare

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    CO2 Laser Ablation• Treatment of choice for CIN in 1980s• Excellent for large cervical lesions, vaginal

    lesions, and difficult to access lesions• Clearance rates high

    – Success rates of 90% to 96%, similar to other modalities

    Outpatient laser ablation• Intracervical Block (same as for LEEP):

    – Inject the cervix at the anticipated surgical margin with 1% lidocaine

    TZ xTZ

    x

    xx

    x

    X=injection site

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    Recommended management of CIN 2,3• CIN 2,3 refers to CIN 2 or CIN 3• Both excision and ablation are acceptable for

    women with histological CIN 2,3 and satisfactory colposcopy

    • Ablation is unacceptable for women with histological CIN 2,3 and unsatisfactory colposcopy

    • Hysterectomy is unacceptable as primary therapy for CIN 2,3

    ASCCP Guidelines for Management of CIN , AJOG 2007

    Recommended management of CIN 2,3• Observation of CIN 2,3 with sequential

    cytology and colposcopy is unacceptable • EXCEPT• During pregnancy• In adolescents and young women

    ASCCP Guidelines for Management of CIN , AJOG 2007

    CENTRAL TENETS for management of CIN in adolescents and young women• The underlying risk of cancer is very low• HPV infection and CIN lesions are common at

    the onset of sexual activity• Clearance of HPV is common• Approximately 90% of CIN 1 lesions will regress• Approximately 40% of CIN 2 lesions will regress

    ASCCP Guidelines for Management of CIN , AJOG 2007

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    Recommended management of CIN 2,3 in adolescents and young women

    • Histological diagnosis of CIN 2: observation is preferred but treatment is acceptable

    • Histological diagnosis of CIN 2,3: either treatment or observation for up to 24 months with both colposcopy and cytology every 6 months is acceptable, provided the colposcopy is satisfactory

    • Histological diagnosis of CIN 3 or colposcopy is unsatisfactory: treatment is recommended

    ASCCP Guidelines for Management of CIN , AJOG 2007

    Recommended management of CIN 2,3 in adolescents and young women

    • For observation of CIN 2 or CIN 2,3 lesions, if the colposcopic lesion worsens, or HSIL cytology or high grade lesion persists for 1 year, repeat biopsy is indicated

    • Treatment is recommended if CIN 3 is subsequently diagnosed, or if CIN 2,3 persists for 24 months

    • After 2 consecutive normal/negative cytology results and normal colposcopy, return to routine screening

    ASCCP Guidelines for Management of CIN , AJOG 2007

    Recommended management of CIN 2,3 in pregnancy

    • In the absence of invasion, colposcopy and cytology every 12 weeks is acceptable

    • Deferring reevaluation until at least 6 weeks postpartum is acceptable

    • Repeat biopsy is recommended only if the lesion appears worse or the cytology suggests invasion

    • Diagnostic excisional procedure is recommended ONLY if invasion is suspected

    ASCCP Guidelines for Management of CIN , AJOG 2007

    CASE• 25 year old G0 is referred for a Pap showing

    HSIL• Colposcopy

    Biopsy showed CIN 2,3

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    What would you do next?

    • Follow-up in 6 months with cytology and colposcopy?

    OR• Treat?

    – LEEP– Cone biopsy– Cryotherapy– Laser ablation

    Recommended management of CIN 2,3 in adolescents and young women

    • Histological diagnosis of CIN 2: observation is preferred but treatment is acceptable

    • Histological diagnosis of CIN 2,3: either treatment or observation for up to 24 months with both colposcopy and cytology every 6 months is acceptable, provided the colposcopy is satisfactory

    • Histological diagnosis of CIN 3 or colposcopy is unsatisfactory: treatment is recommended

    ASCCP Guidelines for Management of CIN , AJOG 2007

    CASE• 25 year old G0 is referred for a Pap showing

    HSIL• Colposcopy

    ECC showed CIN 2,3

    What would you do next?

    • Follow-up in 6 months with cytology and colposcopy

    • Treat– LEEP– Cone biopsy– Cryotherapy– Laser ablation

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    CASE• 25 year old G0 is referred for a Pap showing

    HSIL• Colposcopy

    Biopsy showed CIN 2,3

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    Excisional therapy: Loop versus cone

    • Relative contraindications to loop excision are patients in which invasion is suspected or the patients has a gladular abnormality on Pap (atypical glandular cells, adenocarcinoma in situ). The general consensus is that these patients should have a cold knife cone biopsy in order to get optimal information about the margins and depth of invasion.

    Cone Biopsy by Loop Excision• Single pass for transformation zone• Then deeper pass for endocervical canal• Can be safely performed in the office

    Considerations for adolescents • Now screening before the age of 21 (ACOG)• No HPV testing in women

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    Efficacy:Loop Excision versus Cryotherapy

    • Cost is significantly lower for cryotherapy due to pathology charges incurred by analysis of loop tissue

    • Loop has the benefit of possibility of diagnosing microinvasive disease

    • Loop is not associated with prolonged vaginal discharge common after cryotherapy

    Efficacy: Loop excision versus cone biopsy• Randomized prospective study was published in 1999

    comparing cold-knife cone (CKC) to loop excision• N=85 for CKC and 89 for loop• No differences in subsequent development of disease

    (CIN, invasive cancer, ACIS)• No difference in subsequent rates of satisfactory

    colposcopy (46% vs 37% for CKC vs loop)• Complication rates were comparable

    – Major surgical complication: 1 in each group– Rate of delayed bleeding was 9 versus 10% (NS)– Infection rate was 1% in each group

    Mitchell et al, 1998 Obstet Gynecol 92; 737-44